What of the next 25 years?

What of the next 25 years?

FOUNDER’S LECTURE What of the Next 25 Years? James D. Hardy, MD, FACS, Jackson, Mississippi When Paul Jordan invited me to give this year’s Founder...

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FOUNDER’S LECTURE

What of the Next 25 Years?

James D. Hardy, MD, FACS, Jackson, Mississippi

When Paul Jordan invited me to give this year’s Founder’s Lecture, my reaction was one of surprise and of keen pleasure that I had been so honored. My first move was to refresh my memory regarding the lectures of the past. It was quickly apparent that, most often, the honoree had chosen a clinical topic, although on occasion he had selected a philosophic or historical subject. Therefore, since the Society has just completed its first 25 years, and richly eventful ones at that, I elected to survey briefly our origins and some major changes in alimentary tract surgery that have occurred since 1960, and then to pay special attention to what the years immediately before us and those more remote may bring. These changes will involve not only clinical science, but also the type and frequency of operative surgery (and, incidentally, the incomes of alimentary tract surgeons). The first meeting of the Association for Colon Surgery was held in Miami at the Fontainebleau Hotel on June 12,196O. The original idea was conceived by Dr. Robert Turrell. He enlisted the collaboration of Warren Cole at the University of Illinois and John Waugh at the Mayo Clinic. The perceived need for greater attention of general surFrom the Department of Surgery, University of Mississippi Medical Center, Jackson, Mississippi. Requests for reprints should be addressed to James D. Hardy, MD, Department of Surgery, University of Mississippi Medical Center, 2500 North State Street, Jackson, Mississippi 39216-4505. Presented at the 26th Annual Meeting of the Society for Surgery of the Alimentary Tract, New York, New York, May 14-15. 1965.

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geons to colorectal surgery was the primary objective in forming the Association. I served as program chairman, but it proved difficult to develop a scientifically challenging program devoted only to the colon. There were simply not enough physiologic aspects involved. Therefore, when I was reappointed program chairman, I wrote President Warren Cole that we could organize a much more attractive group of papers if we included the entire alimentary tract and its tributaries. In fact, I wrote, “Why not change the name of our group to the Society for Surgery of the Alimentary Tract?” Dr. Cole was sympathetic, but cautioned that nothing should be done until the matter could be presented to the membership at the next meeting. This was done, the recommendation was accepted, and the constitution and bylaws were changed, as reflected in a letter to me from Claude Welch. “New” Surgical Dlseases and Better Understanding of “Old” Ones Necrotizing enterocolitis of the newborn is a virtually new disease. To be sure, numerous other disorders are virtually new in the past 25 years, but necrotizing enterocolitis has been made possible through the remarkable strides achieved in the life support modalities that permit survival of premature infants who formerly died at birth. Thus, this is a disease that has come about through therapeutic progress. Scarcely less novel has been the common demon-

The American Journal of Surgery

What of the Next 25

stration of arteriovenous malformations in the alimentary tract, especially in the gastroduodenal areas and in the right side of the colon, but also throughout the alimentary tract in some patients. This advance has been made possible through the development of truly sophisticated arteriography. Other major advances include the APUD hormonal peptide series and the unfolding story of esophageal motility disorders. Numerous other examples could be cited, but these will suffice. Clinical and laboratory progress has rendered gastrointestinal research one of the most fascinating and fruitful fields of clinical investigation today. Advances in Dlagnosls and Treatment Progress in the diagnosis and treatment of wellknown diseases has been most gratifying. The most spectacular advances in diagnosis include the incredible sensitivity of Yalow and Rerson’s immunoassay for alimentary tract hormones, the still unfolding dimensions of flexible endoscopy, and the explosive advances in radiologic imaging methods, including arteriography, ultrasonography, nuclear scans, computerized axial tomography and, now at hand, nuclear magnetic resonance. Immunoassays have disclosed that the gastrointestinal tract and its tributaries apparently represent the major endocrine organ in the body. Many new hormones have been identified, some without a demonstrated function thus far. In addition, prostaglandin therapy has barely reached the point of clinical applications. Flexible endoscopy has revolutionized gastroenterology and the diagnosis and management of many gastrointestinal disorders that the surgeon may no longer be called upon to treat. Acute peptic ulcer bleeding visualized at endoscopy, if not controlled by traditional therapy plus H2 blockers such as cimetidine or ranitidine, may be managed by the internist using the heater probe, use of the laser having declined due to the complications of its use. Using endoscopic visualization of the papilla of Vater, the internist may remove common bile duct stones after sphincterotomy, dilate a common duct stricture, or place a permanent stent through an obstructing cancer of the pancreatic ampulla or higher in the common duct. Colonic polyps that might once have required a laparotomy are now commonly removed through the colonoscope. The site of colonic hemorrhage may be more accurately diagnosed with the colonoscope than with a barium enema, although these modalities often complement each other. Radiologic advances are by no means limited to diagnosis. As noted, using radiologic guidance, common duct stones may be removed either in a retrograde fashion through the ampulla, through a T

Volume 151, January 1999

Years?

tube, or percutaneously. Under fluoroscopic guidance and using invasive radiologic techniques, intraabdominal collections of pus or pancreatic pseudocysts may be drained. A bleeding artery causing hematobilia may be embolized. Percutaneous gastrostomy is commonly achieved. All these new procedures diminish the length of the surgeon’s operating schedule. Total parenteral nutrition has long been a routine and an immensely valuable means of supporting patients with small bowel fistulas, peritonitis and ileus, short gut syndrome, inflammatory bowel disease, and other disorders. The peace of mind that parentetal nutrition affords the surgeon even exceeds that provided by the advent of the radiologic technique of #extracting the overlooked common duct stone or the injection of [email protected] to correct the voice after a recurrent nerve injury at thyroidectomy. Staplers, especially promoted by Ravitch in this country, have proved very useful in many aspects of gastrointestinal surgery. As a last example, perforated colonic diverticulitis, so long managed by proximal transverse colostomy and simple drainage of the still-leaking phlegmon, is now much more effectively treated by the Hartmann procedure, with a markedly reduced mortality rate. This example, achieved solely through continued clinical experience and evolution, reminds us that it is not always necessary to create a new technologic advance or laboratory procedure. During the past year, three existing modalities have assisted my own practice or enhanced my knowledge: the use of barium enema to exclude obstructive appendicitis where the diagnosis was in serious question, roentgenography of a centrifuged urine specimen after barium enema to demonstrate the otherwise undiagnosed vesicocolic fistula, and the intraoperative production of a visualized and lasting diverticula in the transverse colon by squeezing solid feces toward a colostomy. Other POtentially significant observations lie all around US, if we could perceive the significance of them.

Unsohfed Problems Many major diseases within the purview of the surgeon, however, remain largely unsolved. These include cancer of most of the alimentary tract; hemorrhagic pancreatitis and its severe complications; cirrhosis with portal hypertension, esophageal variteal bleeding, and terminal hepatic failure; intraabdominal sepsis; vascular accidents involving the intestine; the hepatorenal syndrome with multiple organ failure; and inflammatory bowel disease. Each of these examples of unsolved problems offers a grim reminder that what we know is overshadowed by what we still do not know.

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Hardy

Predktkm of Thhgs to Come: The Next 25 Years Many years ago, I received from the national office of the American Physiological Society, a set of instructions to the essayists at the forthcoming spring meeting. In essence, the message was, be brief, be crisp and, if possible, be interesting! It was emphasized that speculation was encouraged. In that spirit, I offer some thoughts on specific challenges we face. _ Genetics: Few weeks pass without the appearance of additional evidence of the extent to which disease processes are influenced by genetic factors which, theoretically, could someday be corrected by genetic engineering. For example, I have been told by a geneticist that, theoretically, the gene that transmits the devastating illness, multiple familial polyposis, could be replaced with a normal gene and the sperm or ovum then employed in reproduction. The sperm or ovum in the Petri dish would be entered by the corrective gene on a penetrating carrier or vector. Thereafter, the offspring would not have, or transmit, the polyposis gene to future generations. Such investigations are apparently already in progress with respect to farm animals. Similarly, the oncogene that carries the trait that predisposes to breast cancer from mother to daughter, for example, might be replaced by a normal gene. Of course, genetic and environmental factors both enter into the development of many cancers. Genetic studies will unquestionably provide a better understanding of the hereditary trait in diabetes. The genetic aspects of the multiple endocrine neoplasia syndrome continue to unfold. Moreover, there are probably genetic factors, as well as cultural and environmental factors, at work in the development of obesity. Thus, exciting possibilities loom before us in this field. The endocrine system: It would be rash to assume that, in the face of the massive progress of the last 25 years, the ultimate dimensions and dynamics of the endocrine system have been approached. They have not. Only now have we fully embraced the incredibly intimate relationships between the neurotransmitters, on the one hand, and the chemical transmitters on the other (if, indeed, one may consider them separately). Then there are the temporal and cyclic variations in the magnitude of endocrine functions. For example, why do insulinomas, gastrinomas, and pheochromocytomas function differently at different times, and hardly function at all in some patients? Why does the same tumor originally secrete only insulin and then, years later, begin secreting gastrin as well? The brain and alimentary tract: By now, we all know that, in effect, the brain is an endocrine organ that even secretes some of the hormones secreted by

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other(?) organs of the alimentary tract-not just by the pituitary gland, but also by the hypothalamus and, I firmly believe, the higher centers as well. In other words, that semipermeable sac, the skin, encloses a seething neuroendocrine and circulatory transmission system that supports life. It is noteworthy, how many of our common alimentary tract functional disorders can be virtually traced to stress imposed on the brain: spasm of the esophagus, with difficulty in swallowing after a prolonged period of stress; peptic ulceration; diarrhea; and possibly, inflammatory bowel disease. There are still other cases in which stress contributes to surgically important disease, such as alcoholism and hepatic cirrhosis. The individual complexity of the “wiring” of the human brain would, by comparison, place tissue typing in the Stone Age and blood typing long before that. Cancer of the alimentary tract: It is perhaps here that the greatest need for progress exists; cure rates have not improved significantly for esophageal, gastric, pancreatic, hepatic, or colorectal cancer in decades. The complexity of oncogenesis and the infinite variations that may be met in neoplasia render it highly unlikely that one or even several great breakthroughs in knowledge will solve this problem. Rather, in my judgment, this war will be won by attrition, by unrelenting and prolonged research over many decades and even beyond; however, perhaps it is appropriate to suggest the specific directions in which research, or even the application of current knowledge, might be fruitful in diminishing the problem posed by cancer of the alimentary tract. The role of immunodeficiency in oncogenesis is ever more apparent. Worldwide epidemiologic studies in oncogenesis, such as those involving alcohol intake, smoking, diet, and genetic predisposition in esophageal cancer, and fiber and fat intake in colon cancer, are very promising. In the United States, the cause of gastric and pancreatic cancer has thus far remained obscure. Few environmental relationships are as clear as that of cigarette smoking to lung cancer. Genetic studies of cancer-prone families, although perhaps not as clearly germane to moat alimentary tract cancers as to cancers of the breast, may eventually disclose a predisposition which, when combined with an environmental factor, can result in malignant neoplasia. Prevention of alimentary tract cancer should logically follow the revelations of these epidemiologic and genetic investigations. Chemotherapy for solid tumors of the alimentary tract, formally begun after a meeting at the National Institutes of Health in 1956, thus far has not realized the progress achieved for cancers of the urogenital tract, such as Wilms’ tumor, chorionepithelioma, and malignancies of the testis. However, taking as a reference point the almost nonexis-

The American Journal 01 Surgery

Whatof the Next25 Years? tent success reported before our Society was established, it is reasonable to anticipate that effective chemotherapeutic agents will eventually be discovered that will join surgery and radiotherapy in the management of alimentary tract malignancies. Meanwhile, experimental opportunities abound; for example, it is likely that the existing tumor markers that assist in both diagnosis and follow-up will be joined by an increasing array of such modalities. The systemic effects of nonendocrine tumors, an almost unknown territory 25 years ago, have been revealed by determined investigation. Doubtless, a considerable variety of chemical substances are released into the bloodstream by gastrointestinal cancers, substances that collectively result in classic cachexia. Thus, immunodiagnosis of human malignancy may permit earlier treatment and improve upon it. In still another direction, it has been shown that resection of 50 percent of the small bowel has a different effect from a 50 percent bypass in influencing experimental colon cancer in rats [I]. This not only shows that reducing the amount of effective small bowel influences experimental cancer but also that the effects of resection and bypass are different, which suggests that a different mechanism be investigated. Beuchamp et al [Z] have demonstrated atrophic effect of gastrin on experimental colon cancer in mice that was inhibited by a gastrin receptor inhibitor. Inflammatory bowel disease: The etiologic factors involved in Crohn’s disease and idiopathic ulcerative colitis have been investigated and debated for decades. Psychiatric considerations have been advanced, as well as infective agents, and more recently, an immunologic factor has gained some experimental support. It is safe to say, however, that the cause or causes of these diseases, or of this disease with two usually distinctive manifestations, remain obscure. Intraperitoneal sepsis: Gradual progress has been made in the management of intraperitoneal sepsis, which is still a major cause of death for patients on alimentary tract surgical services. Nuclear scans and ultrasonography have afforded some assistance in the detection of purulent collections, and the advent of the computerized axial tomographic scan has proved still more discriminating. Nonetheless, each and all of these imaging procedures often fail to disclose pus which may later be found at autopsy. Radiologic guidance has permitted percutaneous drainage of many abscesses more easily than might have been expected. What the present clinical experimental approach, employing intraperitonetil packing with the abdominal wound left open for repeated trips to the operating room for reassessment, will contribute to the management of intraperitoneal sepsis remains to be seen. I suspect

Volume 151, January 1996

the problem of intraperitoneal sepsis will probably prove a stubborn one to solve.

Is The Alimentary Tract Surgeon An Endangered Species? Many procedures that were commonly performed by the alimentary tract surgeon and which, incidentally, provided significant income, have become either obsolete, much less frequently performed, or “lost” to the radiologist, the gastroenterologist, or both. Gastric freezing for peptic ulceration was probably the shortest lived, most widely applied modality in my memory. More recently, jejunoileal bypass for morbid obesity has been replaced by various types of gastric operations not attended by the numerous metabolic complications of jejunoileal bypass. Gastric surgery for the complications of peptic ulceration has decreased markedly, either because of the effective Hz blockers such as cimetidine or ranitidine or the decrease in the incidence of peptic ulceration due to unknown factors. The removal of asymptomatic gallstones is increasingly frowned upon. Much of alimentary tract endoscopy, whether for gastrointestinal bleeding or for colonic polyps, is now being performed by internists. Decompression of the biliary tract and even palliative treatment of ampullary carcinoma, may be handled without surgical consultation, as may the drainage of a pancreatic pseudocyst or the performance of a gastrostomy. Common bile duct stones may be removed by endoscopic retrograde cholangiopancreatography or by the percutaneous approach. Gallbladder stones containing calcium have been pulverized with sonic waves, as have kidney stones. Exploratory laparotomy for the diagnosis of tumor may be bypassed with fine needle biopsy under the guidance of fluoroscopy and computerized axial tomography. Even abdominoperineal resection for a small, distal rectal carcinoma may be replaced by local excision and radiotherapy in selected instances. Truly, the alimentary tract surgeon now stands at the crossroads. What are his options? Like the adaptive coyote, the general surgeon must adapt himself to the support afforded by the new territory, even if smaller “litters” are required. Then what does lie ahead for the surgeons of our Society? Overall, the future is bright with opportunities over the next 25 years. To begin with, we are all physicians and scientists first, and the advances in physiology and biochemistry that will occur during the future decades will be vast indeed. Clearly, much of the general surgery currently performed will be required for years to come for cancer, gut obstructions and gangrene, certain functional lesions of the

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Hardy

esophagus, complications of peptic ulceration or inflammatory bowel disease, symptomatic gallstones, trauma, and metabolic procedures, such as manipulations for morbid obesity or reduction of hyperlipidemia. Organ Transplantation Organ transplantation is already claiming the increasing attention of cardiac surgeons, as kidney transplantation has now been at center stage for almost 30 years. Transplantation of the liver, brought to clinical fruition by Starzl and Calne and others, is increasingly looked upon as a feasible form of treatment for end stage hepatic failure, malignant neoplasms, and certain metabolic diseases. However, Iwatsuki and associates [3] have recently described 48 patients with primary liver malignancies treated with liver replacement. They found liver transplantation to be ineffective as a form of cancer therapy for most primary malignant tumors. The best results were obtained when the tumors were discovered secondary to underlying hepatic diseases, or if the lesion was a fibrolamellar hepatocellular carcinoma. Now that operative technique and perioperative support have been reasonably well worked out, it may be anticipated with confidence that clinical liver transplantation will be commonly and widely performed in the future. The pancreas: There are approximately 5 million known diabetic persons in the United States, and probably another 5 million are undiagnosed. Successful transplantation of the pancreas would afford management of this disease, which is the leading cause of blindness in this country. Currently available techniques of insulin regulation also do not afford satisfactory protection from the other major complications of diabetes mellitus (renal failure, premature atherosclerotic vascular disease, and peripheral neuropathy). Actually, given the complexity of diabetes, even perfect control of blood glucose levels, thereby avoiding ketoacidosis, and successful transplantation of the pancreas might not prevent all these complications. There is experimental evidence that has been obtained in rodents that successful transplantation of the pancreas will not only prevent the development of these complications, but will reverse some of these induced complications [Orloff MI: personal communication]. This evidence is supported by several clinical studies. The largest clinical experience is probably that at the University of Minnesota, where Sutherland et al [4] have recently reported 100 pancreas allotransplants in human subjects. Thus far, the long-term success achieved in human subjects has been limited, but results have been gradually improving. The spleen: The spleen is not usually considered

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an organ of the alimentary tract, but if transplantation of the spleen becomes common, the general surgeon will be involved. There has long been interest in the splenic content of antihemophilic globulin should splenic transplantation be successfully performed in the hemophilic patient. Fortunately, until recently, commercially available antihemophilic globulin has sufficed, although there was a risk of hepatitis associated with it. Recently, however, with the increasing incidence of the acquired immunodeficiency syndrome and the attendant risk of pooled plasma, there has been some renewed interest in transplantation of the spleen for this purpose. To be sure, before successful splenic allotransplantation becomes clinically feasible, antihemophilic globulin may be produced by bacteria through monoclonal antibody techniques. Incidentally, Lewis et al [5] have recently reported the “cure” of hemophilia by liver transplantation. The small bowel: Technically, transplantation of the small bowel is readily feasible. In 1969, our group [S] transplanted three feet (90 cm) of upper ileum from a mother to her 8 year old son, whose mesenteric small bowel was resected for gangrene due to volvulus. Autologous transplantation using blood vessel anastomoses has been used sporadically for many years, especially recently, in order to bridge esophageal defects; however, small bowel allografts have not had long-term success to date. One major problem is that the gut transplant, like the lung transplant, commonly involves large numbers of bacteria, in contrast to the kidney and the heart. Nonetheless, allotransplantation of the small bowel will eventually become more successful, and a modality will then be available for management of the short bowel syndrome, total aganglionosis, absorptive abnormalities, and metabolic diseases. Summary The early history of the Society for Surgery of the Alimentary Tract has been reviewed, and the remarkable progress in gastrointestinal surgery over the first 25 years of its existence has been acknowledged. The challenging dimensions of the problems that remain unsolved have been emphasized, and the directions that fruitful research may take in the next quarter century have been suggested. The alimentary tract surgeon will be called upon to adapt to change, and to move into new fields of clinical physiology and surgery. The discoveries and progress to be anticipated in the years to come are vast. References 1. Scudamore CH, Freeman HJ. Effects of small bowel transection, resection, or bypass in 1,2dimethylhydrazine-induced rat intestinal neoplasia. Gastroenterology 1983;84:725-31.

The American Journal of Surgery

Whet of the Next 25 Years?

2. Beuchamp RD, Townsend CM Jr, Glass EJ, Thompson JC. Proglumide, a gastrin-receptor antagonist, inhibits growth of colon cancer and enhances survival In mice. Ann Surg 1985; 202:303-g. 3. lwatsuki S, Shaw BR Jr, Gordon RD, Starzl TE. Role of liver transplantation in cancer therapy. Ann Surg 1985; 202:401-407. 4. Sutherland DER, Goetz FC, Najarian JS. One hundred pancreas

Volume 151, January 1986

transplants at a single institution. Ann Surg 1984; 200:414-40. 5. Lewis JH, Bontempo FA, Spero JA, Raghi MV, Starzl TE. Liver transplantation in a hemophiliac. New Engl J Med 1985; 312:1189. 6. Alican F, Hardy JD, Cayirli M, et al. Intestinal transplantation: laboratory experience and report of a clinical case. Am J Surg 1971;121:150-9.

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